Pediatric cardiomyopathy is a heterogeneous genetic disease with high morbidity and mortality in which children often present with fulminant disease leading to death or transplant. The long term goal of this project is to identify the genetic factors that determine the development and progression of cardiomyopathy in order to improve prevention, surveillance, early management, and prognosis. The specific aims of this study are 1) to identify the disease causing and disease associated genetic variants underlying pediatric cardiomyopathy in a carefully phenotyped cohort and 2) to identify genotype-phenotype correlations that allow for risk stratification and improve management and therapy. Exome sequencing will be used as part of a tiered genetic analysis in a large cohort of pediatric cardiomyopathy subjects with systolic (dilated cardiomyopathy) or diastolic (hypertrophic or restrictive cardiomyopathy) dysfunction. This study will significantly increase our understanding of pediatric cardiomyopathy by defining the prevalence of mutations in genes known to cause cardiomyopathy as well as identifying novel disease causing genes in the pediatric population. Genetic association tests will identify variants that modify disease. Novel bioinformatics and systems biology applications for interpretation of exome level genetic information will contribute fundamental knowledge and technical innovation to the translation of genomic data to clinical utility. These aims will provide critical genetic architecture data, identify variants with large effects, and enable genotype-phenotype correlations necessary for advancing management and therapy.